DESCRIPTION: (Applicant's abstract) The overall goal of this proposal is to determine the relation between the organization of centrally generated locomotor commands and known patterns of recurrent inhibition, and to investigate two sets of mechanisms that may determine the effect of this inhibition on motoneuron pools during locomotor and postural activity. Recent work from this laboratory suggests that: 1) the Renshaw cells which inhibit synergistic motor nuclei may form a network of interneurons linked by mutual inhibition; 2) the recurrent inhibition produced by Renshaw cells may affect the activity of motoneurons through synaptic interactions in the dendritic trees of motoneurons; and 3) the distribution of Renshaw inhibition is correlated with the distribution of locomotor commands to motor nuclei that innervate proximal limb muscles. Studies have been planned for this proposal to address three aims related to these observations. The first specific aim is to test the hypothesis that Renshaw cells activated by synergist groups of motoneurons are mutually inhibitory. If this hypothesis is confirmed, the strength and distribution of this mutual inhibition will be determined. The second specific aim is to determine the location of synaptic and intrinsic currents within the dendritic arbors of motoneurons. In these studies, interactions between Renshaw inhibition and several synaptic and intrinsic currents in motoneurons will be examined. The third specific aim is to compare the patterns of synaptic potentials to different functional groups of motoneurons during locomotor activity. These studies will address several issues concerning the central organization of locomotion, its relation to the organization of recurrent inhibition, and ability of correlation methods to assess the organization of spinal locomotor commands. Renshaw inhibition is associated with most motoneuron pools of limb muscles, and its regulation is compromised by spinal injury and upper motoneuron disease. The proposed studies will provide information on the control of the activity in motoneuron pools by Renshaw inhibition and the implications of disruption by disease or injury of control of this spinal system.